Long-term effect of flunarizine on patients with alternating hemiplegia of childhood in Japan

To determine the effect of flunarizine therapy on patients with alternating hemiplegia of childhood (AHC), we sent a questionnaire by mail to council members of the Japanese Society of Child Neurology. We collected 28 AHC patients, and studied their clinical courses and the effects of drug therapy. All of the patients had received flunarizine. In 18 of the 28 patients, flunarizine reduced the severity, duration, or frequency of the hemiplegic attacks. No other drug was more effective than flunarizine. Some flunarizine non-effective patients were severely deteriorated, for example, they had dementia or were ventilator-assisted. Flunarizine had not only a short-term effect, i.e. it reduced the hemiplegic attacks, but also a long-term effect on the motor and intellectual development in some patients with AHC. Flunarizine is still an essential drug for treating AHC.     

Long-term follow up of an adult with alternating hemiplegia of childhood and a p.Gly755Ser mutation in the ATP1A3 gene

Alternating hemiplegia of childhood (AHC) is a rare neurological disease mainly caused by mutations in the ATP1A3 gene and showing varied clinical severity according to genotype. Patients with a p.Gly755Ser (p.G755S) mutation, one of minor genotypes for AHC, were recently described as having a mild phenotype, although their long-term outcomes are still unclear due to the lack of long-term follow up. Here, we demonstrate the full clinical course of a 43-year-old female AHC patient with p.G755S mutation. Although her motor dysfunction had been relatively mild into her 30?s, she showed a subsequent severe aggravation of symptoms that left her bedridden, concomitant with a recent recurrence of seizure status. The seizures were refractory to anti-epileptic drugs, but administration of flunarizine improved seizures and the paralysis.Our case suggests that the phenotype of AHC with p.G755S mutation is not necessarily mild, despite such a presentation during the patient’s younger years.     

儿童交替性偏瘫六例分析

目的探讨儿童交替性偏瘫（ＡＨＣ）的临床特点及治疗方法。方法对６例ＡＨＣ患儿的临床资料进行分析。结果６例患儿的临床特征为出生后１８个月起内病，频繁发作，持续数分钟至数小时；短暂的眼球震颤，肌张力异常，舞蹈徐动样动作，植物神经机能紊乱和认知机能减退；睡眠可缓解无力及锥体外系症状。应用氟桂嗪治疗后，１例患儿发作完全停止，其余５例患儿均显示发作频率和持续时间降低。结论本病的主要特征为１８个月内起病的发作性交替性偏瘫，伴锥体外系症状及智力障碍，氟桂嗪治疗本病有效     

Alternating Hemiplegia of Childhood With a de Novo Mutation in ATP1A3 and Changes in SLC2A1 Responsive to a Ketogenic Diet

BackgroundAlternating hemiplegia of childhood (AHC) is a rare condition characterized by an early onset of hemiplegic episodes and other paroxysmal or permanent neurological dysfunctions. Recently, mutations in the ATP1A3 gene have been identified as the causal mechanism of AHC. Regarding the differential diagnosis of AHC, glucose transporter 1 deficiency syndrome may be considered because these two disorders share some paroxystic and nonparoxystic features.Patient and resultsWe report a typical case of AHC harboring a de novo mutation in the ATP1A3 gene, together with a duplication and insertion in the SLC2A1 gene who exhibited marked clinical improvement following ketogenic diet.ConclusionBecause the contribution of the SLC2A1 mutation to the clinical phenotype cannot be definitely demonstrated, the remarkable clinical response after ketogenic diet led us to the hypothesis that ketogenic diet might be effective in AHC as it provides an alternative energy source for the brain.     

Successful trial of amantadine hydrochloride for two patients with alternating hemiplegia of childhood

We report here the efficacy of amantadine hydrochloride for two patients with alternating hemiplegia of childhood (AHC) that did not respond to flunarizine. Amantadine was administered to one patient at age one year and seven months and to the other at age 25 years. The frequencies and duration of the hemiplegic attacks significantly improved in both patients. However, the attacks gradually returned to the previous level after a significant reduction in seizures for three years in the younger patient with ongoing AHC. Our therapeutic results further support the hypothesis that glutamate and NMDA receptors are involved in inducing alternating hemiplegic attacks, because amantadine as well as its derivative, memantine, are clinically available non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, with neuroprotective effects. Amantadine is worth trying when treating patients with AHC as a first trial or a substitute for flunarizine once the latter agent looses effect.     

黛力新联合氟桂利嗪防治偏头痛的Meta分析

目的系统评价黛力新(氟哌噻吨美利曲辛)联合氟桂利嗪防治偏头痛的有效性和安全性。方法计算机检索Embase、Pubmed、Cochrane图书馆临床对照试验资料库、CNKI、维普及万方数据库,纳入黛力新联合氟桂利嗪防治偏头痛的随机对照试验文献(randomized controlled trials,RCT),按Cochrane系统评价的方法评价纳入研究质量,并使用Rev Man 5.1软件对纳入研究进行Meta分析。结果最终纳入符合条件的文献10篇,包括932例患者。Meta分析结果显示,黛力新联合氟桂利嗪组与氟桂利嗪组比较差异有统计学意义[OR=4.23,95%CI(2.90,6.17),P0.00001]。联合用药的不良反应与单独使用氟桂利嗪无明显差异[OR=1.14,95%CI(0.58,2.26),P=0.70]。结论现有限研究表明,黛力新联合氟桂利嗪防治偏头痛效果优于与单纯使用氟桂利嗪,且安全性良好。但本系统评价纳入文献数量有限,质量较低,尚需开展更多设计合理、执行严格的多中心大样本的随机对照试验验证其疗效及安全性。     

Topiramate: a new agent for patients with alternating hemiplegia of childhood

Alternating hemiplegia of childhood is a rare syndrome characterized by the onset, before 18 months of age, of frequent attacks of alternating paralysis. Here we report the efficacy of topiramate in four patients with alternating hemiplegia of childhood (AHC) that did not respond to flunarizine, as well as in two newly diagnosed patients. Following treatment with topiramate, the frequency and duration of hemiplegic attacks significantly improved in all patients. Additional symptoms such as seizures, migraine, involuntary movements, autonomic symptoms, and impaired mental development also improved. Topiramate is worth trying when treating patients with AHC as a first trial, or a substitute for flunarizine once the latter agent loses effect.     

Differences in odor identification among clinical subtypes of Parkinson’s disease

Objective: Olfactory dysfunction is a non‐motor symptom in idiopathic Parkinson’s disease (PD). We investigated whether this dysfunction differs among clinical subtypes of PD. Methods: Participants comprised of 90 patients with idiopathic PD and without dementia. Olfactory function was evaluated using the odor stick identification test for Japanese, which evaluated the detection of 12 odorants familiar to Japanese participants. Patients were divided into tremor‐dominant type (TDT), akinetic‐rigid type (ART), and mixed type (MXT) PD subgroups using part III of the Unified Parkinson’s Disease Rating Scale. Results: Fifty‐five patients were classified as ART, 21 as MXT, and 14 as TDT. There were no differences in age, sex, or duration of illness among the subtypes. Subjective symptoms of impaired sense of smell were significantly higher (P < 0.05) in the ART than in the TDT. Mean odor identification score was 4.3 in the ART, 5.2 in MXT, and 6.6 in TDT. It was significantly lower in the ART than in the TDT (P < 0.01). Conclusion: Olfactory dysfunction differed among the clinical subtypes of PD. This suggests that olfactory function might relate to prognosis of patients with PD.     

Intragenic mutations in SMN1 may contribute more significantly to clinical severity than SMN2 copy numbers in some spinal muscular atrophy (SMA) patients

Background: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by deletion or intragenic mutation of SMN1. SMA is classified into several subtypes based on clinical severity. It has been reported that the copy number of SMN2, a highly homologous gene to SMN1, is associated with clinical severity among SMA patients with homozygous deletion of SMN1. The purpose of this study was to clarify the genotype-phenotype relationship among the patients without homozygous deletion of SMN1. Methods: We performed molecular genetic analyses of SMN1 and SMN2 in 112 Japanese patients diagnosed as having SMA based on the clinical findings. For the patients retaining SMN1, the PCR or RT-PCR products of SMN1 were sequenced to identify the mutation. Results: Out of the 112 patients, 106 patients were homozygous for deletion of SMN1, and six patients were compound heterozygous for deletion of one SMN1 allele and intragenic mutation in the retained SMN1 allele. Four intragenic mutations were identified in the six patients: p.Ala2Val, p.Trp92Ser, p.Thr274TyrfsX32 and p.Tyr277Cys. To the best of our knowledge, all mutations except p.Trp92Ser were novel mutations which had never been previously reported. According to our observation, clinical severity of the six patients was determined by the type and location of the mutation rather than SMN2 copy number. Conclusion: SMN2 copy number is not always associated with clinical severity of SMA patients, especially SMA patients retaining one SMN1 allele.     

Motor subtype changes in early Parkinson's disease

IntroductionDistinct motor subtypes of Parkinson's disease (PD) have been described through both clinical observation and through data-driven approaches. However, the extent to which motor subtypes change during disease progression remains unknown. Our objective was to determine motor subtypes of PD using an unsupervised clustering methodology and evaluate subtype changes with disease duration.MethodsThe Parkinson's Progression Markers Initiative database of 423 newly diagnosed PD patients was utilized to retrospectively identify unique motor subtypes through a data-driven, hierarchical correlational clustering approach. For each patient, we assigned a subtype to each motor assessment at each follow-up visit (time points) and by using published criteria. We examined changes in PD subtype with disease duration using both qualitative and quantitative methods.ResultsFive distinct motor subtypes were identified based on the motor assessment items and these included: Tremor Dominant (TD), Axial Dominant, Appendicular Dominant, Rigidity Dominant, and Postural and Instability Gait Disorder Dominant. About half of the patients had consistent subtypes at all time points. Most patients met criteria for TD subtype soon after diagnosis. For patients with inconsistent subtypes, there was an overall trend to shift away from a TD phenotype with disease duration, as shown by chi-squared test, p < 0.001, and linear regression analysis, p < 0.05.ConclusionThese results strongly suggest that classification of motor subtypes in PD can shift with increasing disease duration. Shifting subtypes is a factor that should be accounted for in clinical practice or in clinical trials.     

Impact of DSM-5 Changes on the Diagnosis and Acute Treatment of Schizophrenia

Objective:To examine the consequences and validity of changes in Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 diagnostic criteria for schizophrenia, eg, omission of subtypes, using a large dataset of double-blind, randomized, placebo-controlled schizophrenia trials.Methods:Data from 22 short-term efficacy registration trials of second generation antipsychotics for the treatment of acute psychotic episodes in patients with schizophrenia (N = 5233), submitted to the Dutch regulatory authority were analyzed. We examined whether patients in these pre-DSM-5 trials met the diagnostic criteria for schizophrenia according to DSM-5. Using linear regression, we examined differences in effect size between DSM-IV subtypes and between DSM-5 symptom dimensions.Results:Over 99.5% of the patients met DSM-5 diagnostic criteria for schizophrenia and no differences in effect size were found between schizophrenia subtypes (P = .65). Symptom dimensions that respond best to treatment with second generation antipsychotics were hallucinations, delusions, disorganized speech, and mania (Hedge’s g −0.23 to −0.31).Conclusions:Results of clinical trials in patients with pre-DSM-5 schizophrenia also apply to patients diagnosed with DSM-5 schizophrenia. Omission of the classic subtypes is justified as they are not predictive of response to treatment. The DSM-5 C-RDPSS scale adds valuable information to the categorical diagnosis of schizophrenia, which is relevant for antipsychotic response.Key words: antipsychotics, clinical trials, diagnostic criteria     

Behavioral assessment of Japanese children with epilepsy using SDQ (strengths and difficulties questionnaire)

The aim of this study was to elucidate the availability of the strengths and difficulties questionnaire (SDQ) as a screening tool for identifying behavioral problems in Japanese children with epilepsy. Methods: Eighty-three 4–16 year-old epileptic patients, followed at Tanabe-Kadobayashi Children’s Clinic, were studied. Children with severe mental or physical disability were excluded. The Japanese version of the SDQ was used, and scores were compared to the Japanese standard. Results: ‘Hyperactivity’ was the SDQ category with the most striking differences from normal: a significant numbers of children had scores above the clinically normal range and only a small proportion were within the normal range (p < 0.0001). The rates of epilepsy patients with scores above normal range were also significantly higher for ‘peer problems’ and ‘conduct problems’ (p < 0.0001 and p < 0.01). The rates of epilepsy patients with scores within the normal range was significantly lower for ‘emotional symptoms’ than in normal controls (p < 0.001). On the other hand, the ‘pro-social behavior’ score did not differ significantly from the Japanese standard. As for clinical factors, patients with symptomatic localization-related epilepsy and focal electroencephalographic abnormalities had significantly higher scores for some SDQ items. Age at epilepsy onset correlated negatively with scores for ‘total difficulties’ and ‘hyperactivity’, suggesting early onset to be a risk factor for poor SDQ scores. Conclusions: These findings confirm that higher rates of psychiatric comorbidity in Japanese children with epilepsy may be diagnosed using SDQ in Japanese children with epilepsy. These problems should be addressed in the early phase of epilepsy management in order to preserve health-related quality of life for affected patients.     

A severe form of autosomal recessive spinocerebellar ataxia associated with novel PMPCA variants

Spinocerebellar ataxia, autosomal recessive 2 (SCAR2) [MIM:213200] is a rare autosomal recessive disease of spinocerebellar ataxia associated with degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR2 is characterized by onset of impaired motor development and ataxic gait in early childhood. Recently, several PMPCA gene variants have been reported in SCAR2 patients with mild and non-progressive symptoms. PMPCA codes frataxin, which is crucial for iron biosynthesis in cells. We report a case of a 15-year-old Japanese girl with infancy-onset, very severe and progressive developmental delay, cerebellar ataxia, and extrapyramidal symptoms. Brain magnetic resonance imaging showed cerebellar atrophy and excessive brain iron accumulation in the bilateral globus pallidi and substantia nigra. Based on the clinical phenotypes and imaging, neurodegeneration with brain iron accumulation was suspected. Whole-exome sequencing on the proband and her parents revealed novel compound heterozygous variants at c.667C > T (p.Arg223Cys) and c.853del (p.Asp285llefs*16) in PMPCA. Thus, her disease was diagnosed as SCAR2. Phenotype in our case was different from ones previously reported for SCARs in the points of much severer clinical presentations with extrapyramidal signs and imaging suspected iron accumulation, and might overlap neurodegeneration with brain iron accumulation or NBIA subtypes. Our case might provide a new insight into PMPCA gene-related disorders and expand the disease concept.     

Acute stroke with major intracranial vessel occlusion: Characteristics of cardioembolism and atherosclerosis-related in situ stenosis/occlusion

Acute ischemic stroke with major intracranial vessel occlusion is commonly due to cardioembolic or atherosclerosis-related in situ stenosis/occlusion, and immediate identification of these subtypes is important to establish the optimal treatment strategy. The aim of this study was to clarify the differences in clinical presentation, radiological findings, neurological temporal courses, and outcomes between these etiologies, which have not been fully evaluated. Consecutive emergency patients with acute ischemic stroke were retrospectively reviewed. Among them, patients with stroke with major intracranial vessel occlusion were analyzed with a focus on clinical and radiological findings, and a comparison was performed for those with cardioembolic or atherosclerosis-related in situ stenosis/occlusion. Of 1053 patients, 80 had stroke with acute major intracranial vessel occlusion (45 with cardioembolic and 35 with atherosclerosis-related in situ stenosis/occlusion). Interestingly, the susceptibility vessel sign (SVS) on T2-weighted MR angiography was more frequently detected in cardioembolic stroke (80.0%) than in atherosclerosis (in situ stenosis: 5.9%, chronic occlusion: 14.3%). Moreover, the proximal intra-arterial signal (IAS) on arterial spin labeling MRI and the distal IAS on fluid attenuated inversion recovery MRI was less frequently detected in chronic occlusion (27.3% and 50.0%, respectively) than in acute occlusion due to cardioembolic or in situ stenosis. Multivariate regression analysis showed that the SVS was significantly related to cardioembolism (adjusted odds ratio (OR): 21.68, P = 0.004). Clinical characteristics of acute stroke with major intracranial vessel occlusion differ depending on the etiology. The SVS and proximal/distal IAS on MRI are useful to distinguish between cardioembolic and atherosclerotic-related in situ stenosis/occlusion.     

Classification of amyotrophic lateral sclerosis cases at presentation in epidemiological studies

Abstract Amyotrophic lateral sclerosis (ALS) diagnosis is based exclusively on clinical grounds because of the absence of biological markers and of specific neuroradiological and neurophysiological diagnostic features. A clinical classification system of cases has been introduced (El Escorial Criteria, EEC) and then revised after the inclusion of the neurophysiologic assessment (Airlie House Criteria, AHC) for enrolment of patients in clinical trials. The aim of this study is to present cases at presentation in the early stages of the disease that have difficult allocation both in EEC and AHC. All cases were subjects enrolled through SLAP, a population-based registry based in Puglia, Southern Italy. Although differential diagnosis excluded ALS-mimic syndromes, we identified four cases (out of 130 cases, 3.1%) that did not meet the EEC and AHC at the first visit. Even though the number of unclassifiable cases is small, both EEC and AHC may be restrictive. This precludes the enrolment of ALS cases at an early stage both in observational studies and clinical trials.     

Clinical Risk Factors of Thromboembolic and Major Bleeding Events for Patients with Atrial Fibrillation Treated with Rivaroxaban in Japan

Background: It is important to understand the risk of thromboembolism and bleeding in patients with nonvalvular atrial fibrillation (NVAF) receiving direct oral anticoagulants; however, data on risk factors in Japanese patients are limited. Methods: XAPASS (Xarelto Post-Authorization Safety and Effectiveness Study in Japanese Patients with Atrial Fibrillation) is a prospective observational study examining the safety and effectiveness of rivaroxaban in Japanese real-world clinical practice. We investigated risk factors for stroke/noncentral nervous system systemic embolism (non-CNS SE)/myocardial infarction (MI) and major bleeding using 1-year follow-up data. Associations between baseline characteristics and outcomes were examined by Cox regression analysis. Results: During April 2012-June 2014, 11,308 patients newly started with rivaroxaban treatment were enrolled. Of 9578 patients with 1-year data fixed as of September 2017, 6220 patients who received appropriate dosages of rivaroxaban for their creatinine clearance were included in the present safety outcomes subanalysis, and 6198 were included in the effectiveness outcomes analysis. Stroke/non-CNS SE/MI was observed in 97 of 6198 patients (1.6%, 1.8 events/100 patient-years), and major bleeding occurred in 102 of 6220 patients (1.6%, 1.9 events/100 patient-years). Age greater than or equal to 75 years (hazard ratio [HR]: 2.27; [95% confidence interval (CI): 1.49, 3.47]), prior ischemic stroke/transient ischemic attack (2.08; [1.38, 3.13]), and antiplatelet use (3.23; [1.83, 5.70]) were associated with stroke/non-CNS SE/MI. Creatinine clearance less than 50 mL/min (HR: 1.86; [95% CI: 1.26, 2.75]), diabetes (1.55; [1.02, 2.35]), and antiplatelet use (3.04; [1.70, 5.45]) were associated with major bleeding. Conclusions: These results would help physicians to assess risks in Japanese patients with NVAF receiving rivaroxaban.     

Association study between Disrupted-in-Schizophrenia-1 (DISC1) and Japanese patients with treatment-resistant schizophrenia (TRS)

Treating the 20-30% of patients with schizophrenia whose symptoms are resistant to antipsychotic treatment, a condition known as treatment-resistant schizophrenia (TRS), can be problematic. Recently, an association between Disrupted-in-Schizophrenia-1 (DISC1), a candidate susceptibility gene for schizophrenia, and TRS was reported. Associations between three missense SNPs, rs3738401 (Q264R), rs6675281 (L607F), and rs821616 (S704C) in DISC1, especially rs3738401, showed strong significance. Thus, the main aim of our current study was to examine if the reported possible functional polymorphisms in DISC1 were related to Japanese TRS. First, DISC1 was re-investigated in 485 Japanese patients with schizophrenia and 660 healthy controls with a case-control study using four candidate SNPs, rs751229, rs3738401, rs821597, and rs821616. DISC1 was not associated with schizophrenia in the Japanese population. Second, we investigated whether these SNPs contributed to TRS in 127 inpatients with schizophrenia (35 patients; TRS and 92 patients; non-TRS). The genotypic distributions of these four SNPs were not significantly different between TRS and non-TRS in either genotypic or recessive models of minor alleles. In addition, clinical variables, such as improvement in clinical symptoms, duration of hospitalization, and total antipsychotics dose amounts, were not different among the genotypes of these SNPs. Taken together, results showed that DISC1 had no apparent degree of association with Japanese patients with schizophrenia as a candidate susceptibility gene for disease per se or TRS.     

Total Antioxidant Capacity Predicts Outcome in Acute Ischemic Stroke Subtypes in Egyptian Patients

Background: Oxidative stress after ischemic stroke contributes to neuronal cell injury. We tried to demonstrate an association between total antioxidant capacity (TAC) levels and outcomes after acute ischemic stroke (AIS). Methods: We enrolled 60 patients (36 females and 24 males) who were admitted to our hospital due to AIS, in addition to 30 age and sex-matched healthy controls. TAC levels were measured on day 1 of stroke onset, the relationships between TAC levels, stroke subtypes, and clinical outcomes based on the National Institutes of Health Stroke Scale and modified Rankin scale upon discharge were evaluated. Results: TAC levels were significantly lower in AIS patients than control (P < .001) being much lower in patients with large-vessel cerebral infarction than in those with small-vessel infarction. We investigated whether TAC concentrations reflected the severity and outcome of ischemic stroke and we found a significantly lower concentration of TAC in the poor outcome group than in the good outcome group (P < .001). Conclusions: Our findings suggested that the biochemical changes related to TAC and oxidative stress may be considered a marker of ischemic brain injury and clinical outcome of ischemic stroke.     

Psychopharmacological treatment differences in autogenous and reactive obsessions: A retrospective chart review

Background: Identification of homogeneous subgroups of obsessive compulsive disorder (OCD) patients may have important implications for improving effective treatment options. It has been proposed that obsessive thoughts can be classified into two subtypes, i.e. autogenous and reactive obsessions. Although it has been shown that patients with autogenous obsessions may display a worse response to treatment, no studies have yet addressed whether there is a different need for the psychopharmacological treatment options in the subtypes of OCD patients. Aim: To investigate the clinical characteristics and treatment differences between autogenous (A-OCD) and reactive (R-OCD) subtypes of OCD patients. Methods: Both OCD subgroups (n = 50 for A-OCD, n = 130 for R-OCD) were compared with each other in terms of their demographic and clinical parameters. Odds ratio values for gender, treatment options, co-morbidity, severity of OCD, and response to treatment were computed. Multivariate hierarchical regression analyses were performed to identify any predictors for treatment options, severity of OCD, and response to treatment. Results: Our results indicated that the A-OCD and R-OCD groups differed from each other on some demographic and clinical variables in addition to their psychopharmacological treatment needs. Patients in the A-OCD group were found to be prescribed an atypical antipsychotic 2.3 times more likely than the R-OCD group. The odds for a combination treatment, or the improvement of OCD symptoms from baseline levels did not differ between the two subtypes of obsession groups. Conclusions: Autogenous and reactive subtypes of obsessions may need to be offered different psychopharmacological treatment options.     

Astroglial cell subtypes in the cerebella of normal adults,elderly adults,and patients with Alzheimer's disease: A histological and immunohistochemical comparison

Objectives and experimental design Cerebella of young adults, elderly adults, and patients with Alzheimer's disease (AD) (with and without cerebellar amyloid deposits) were studied by Golgi staining and glial fibrillary acid protein (GFAP) immunocytochemical methods. Observations Three subtypes of Golgi epithelial cells and nine subtypes of stellate neuroglia (both normal and hypertrophic) were defined by their morphology, their GFAP‐reactivity, their specific location in the cortical layers, and their responses in senility and AD. The GFAP immunoreaction was subtype specific. In aged and AD cerebella, different morphological and GFAP‐immunoreactive subtype‐specific changes were observed: in the white matter, the subtypes were always GFAP‐immunopositive, but in the grey matter some astroglial subtypes showed a variable or no increase in GFAP staining. The astrocytes at the limits of the granule cell layer showed more and longer processes. Variations were seen in one or more folia, involving one or more subtypes and affecting different numbers of cells of each subtype. No clear differences were seen in glial reactivity between beta‐amyloid positive and β‐amyloid (Aβ) negative AD cerebella. No important relationships were found between Aβ deposits. In aged and AD cerebella, different subtypes expressed new proteins (APP, calretinin). Conclusions The existence of different glial subtypes in different locations suggests they have different functions. General and local variations in these subtypes suggest that both general and local induction factors must also exist. The responses of glial cells to as‐yet undefined stimuli might lead to general or local neuronal changes important in senility and the pathogenic course of AD. GLIA 2015;63:287–312